AAPS PharmSciTech

, Volume 14, Issue 2, pp 639–648 | Cite as

Formulation and Development of Extended-Release Micro Particulate Drug Delivery System of Solubilized Rifaximin

  • Rohan V. Karanje
  • Yogita V. Bhavsar
  • Kirti H. Jahagirdar
  • Kiran S. Bhise
Research Article


Rifaximin (RFX), a semi-synthetic antibiotic belonging to BCS class IV category, has been used in the treatment of traveler’s diarrhea. An attempt has been made to improve aqueous solubility of RFX in the presence of β-cyclodextrin (β-CD) and hydroxy propyl β-cyclodextrin (HP-β-CD) and control its release in the gut by enteric coating. The stoichiometric proportion of RFX and complexing agent’s β-CD and HP-β-CD were determined by phase solubility studies. RFX–β-CD and RFX–HP-β-CD were prepared in 1:2 ratio by solvent evaporation technique using rota-evaporator with yield of 78% and 84% respectively followed by their evaluation using different techniques such as saturation solubility, Fourier transform infrared, differential scanning calorimeter, powder X-ray diffractometer, in vitro antimicrobial activity. The saturation solubility of RFX had improved from 0.0736 mg/ml to 0.2354 mg/ml and 0.5681 mg/ml in presence of β-CD and HP-β-CD respectively resulting in an increased zone of inhibition in the later complex during antimicrobial studies. The RFX–HP-β-CD complex particles were coated with eudragit L 100 (EL 100) by spray drying technique. The 32 factorial design was applied to formulate the micro particles. All formulations exhibited pH dependant drug release. The % EE was 69% and the release of RFX was retarded by enteric coating in the optimized batch FB2. Therefore, it can be concluded that solubility of some BCS class IV drugs can be improved by β-CD complexation and release of such inclusion complexes can be retarded to increase the residence time of RFX in the gastrointestinal tract.

Key word

cyclodextrin complexes eudragit L100 micro particles rifaximin spray dryer 



Analysis of variance




Biopharmaceutical classification system


Coefficient of correlation


Degree Celsius

% DR

Percentage drug release


Differential scanning calorimeter

% EE

Percentage entrapment efficiency

EL 100

eudragit L 100


Hydroxy propyl β cyclodextrin







PBS pH 6.8

Phosphate buffer solution pH 6.8


Powder X-ray diffractometer






Revolution per minute


Scanning electron microscopy


United state pharmacopeia


  1. 1.
    Martini S et al. Solution structure of rifaximin and its synthetic derivative rifaximin determined by experimental NMR and theoretical simulation methods. Bioorg Med Chem. 2004;12(9):2163–72. doi: 10.1016/j.bmc.2004.02.027.CrossRefPubMedGoogle Scholar
  2. 2.
    Huang DB, DuPont HL. Rifaximin—a novel antimicrobial for enteric infections. J Infect. 50(2): 97–106.Google Scholar
  3. 3.
    Jahagirdar HA. Patent Application No- 20090028940 USPC CLASS: 424468 NO DOI FOR PATENT.Google Scholar
  4. 4.
    Scarpignato C, Pelosini I. Rifaximin, a poorly absorbed antibiotic: pharmacology and clinical potential. Chemotherapy. 2005;51 suppl 1:36–66. doi: 10.1159/000081990.CrossRefPubMedGoogle Scholar
  5. 5.
    Vaira D. Rifaximin suspension for the eradication of Helicobacter pylori. Curr Ther Res. 58(5):300–308.Google Scholar
  6. 6.
    Darkoh C et al. Bile acids improve the antimicrobial effect of rifaximin. Antimicrob agents chemother. 2010;3618–3624. doi: 10.1128/AAC.00161-10.
  7. 7.
    Rawat S, Jain SK. Solubility enhancement of celecoxib using β-cyclodextrin inclusion complexes. Eur J Pharm Biopharm. 2004;57:263–7. doi: 10.1016/j.ejpb.2003.10.020.CrossRefPubMedGoogle Scholar
  8. 8.
    Bidyut N, Amrutansu P, Annapurna MM. Spectrophotometric estimation of rifaximin in pure and tablet dosage form. Int J Pharm Technol. 2010;2(4):1098–104.Google Scholar
  9. 9.
    Loftsson T, Vogensen SB, Desbos C, Jansook P. Carvedilol: solubilization and cyclodextrin complexation: a technical note. AAPS PharmSciTech. 2008;9(2) (# 2008). doi: 10.1208/s12249-008-9055-7.
  10. 10.
    Patel AR, Vavia PR. Preparation and evaluation of taste masked famotidine formulation using drug/β-cyclodextrin/polymer ternary complexation approach. AAPS PharmSciTech. 2008;9(2):544–50. doi: 10.1208/s12249-008-9078-0.CrossRefPubMedGoogle Scholar
  11. 11.
    Waleczeka KJ, Cabral Marquesb HM, Hempelc B, Schmidt PC. Phase solubility studies of pure (2)-a-bisabolol and camomile essential oil with b-cyclodextrin. Eur J Pharm Biopharm. 2003;55(2):247–51. doi: 10.1016/S0939-6411(02)00166-2.CrossRefGoogle Scholar
  12. 12.
    Hirayama F, Uekama K. Cyclodextrin-based controlled drug release system. Adv Drug Deliv Rev. 1999;36:125–41. doi: 10.1016/S0169-409X(98)00058-1.CrossRefPubMedGoogle Scholar
  13. 13.
    Liu L et al. A study on the supramolecular structure of inclusion complex of β-cyclodextrin with prazosin hydrachloride. Carbohydrate polymers, 68(Issue 3):472–476. doi:  10.1016/j.carbpol.2006.11.007.
  14. 14.
    Werner F, Okemo P, Ansorg R. Antibacterial activity of East African Medicinal; plants. J Ethnopharmacol. 60:79–84.Google Scholar
  15. 15.
    Alanazi FK, El-Badry M, Ahmed MO, Alsarra IA. Improvement of albendazole dissolution by preparing microparticles using spray-drying technique. Sci Pharm. 2007;75:63–79.CrossRefGoogle Scholar
  16. 16.
    Liu W, Wu WD, Selomulya C, Chen XD. Uniform chitosan microparticles prepared by a novel spray-drying technique. Int J Chem Eng. 2011;2011. doi: 10.1155/2011/267218. Article ID 267218, 7 Pages.
  17. 17.
    Robinson S. (Melton Mowbray GB), Smith, Susan Stewart (Leicestershire GB). Spray-drying process for the preparation of microparticles; Application Number: 09/342356 Patent no: US 6,451,349 B1.Google Scholar
  18. 18.
    Elshafeey AH, Sami EI. Preparation and in-vivo pharmacokinetic study of a novel extended release compression coated tablets of Fenoterol Hydrobromide. AAPS PharmSciTech. 2008;9(3) (# 2008). doi:  10.1208/s12249-008-9135-8.
  19. 19.
    Narayan P, Marchant D, Wheatley MA. Optimization of spray drying by factorial design for production of hollow microspheres for ultrasound imaging. J Biomed Mater Res. 2001;56(3):333–41. doi: 10.1002/1097-4636(20010905)56:3333::AID-JBM1101>3.0.CO;2-K.CrossRefPubMedGoogle Scholar
  20. 20.
    Tajber L, Corrigan OI, Healy AM. Spray drying of budesonide, formoterol fumarate and their composites—II. Statistical factorial design and in vitro deposition properties. Int J Pharm. 2009;367(1–2):86–96. doi: 10.1016/j.ijpharm.2008.09.029.CrossRefPubMedGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • Rohan V. Karanje
    • 1
  • Yogita V. Bhavsar
    • 1
  • Kirti H. Jahagirdar
    • 1
  • Kiran S. Bhise
    • 1
  1. 1.Department Of PharmaceuticsMCE Society’s Allana College of PharmacyCamp PuneIndia

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